In teenagers, prolonged fatigue was often accompanied by mood or anxiety disorders and was associated with significant levels of disability, researchers found.

Action Points

Note that this cross-sectional study demonstrated an association between mood disorders and prolonged fatigue among adolescents.

Be aware that in the absence of longitudinal data, a causative relationship between fatigue and mood disorders cannot be demonstrated.

In teenagers, prolonged fatigue was often accompanied by mood or anxiety disorders and was associated with significant levels of disability, researchers found.

In a nationally representative sample of adolescents ages 13 to 18, 3% reported having extreme fatigue lasting at least 3 months and about half of those who did also had mood or anxiety disorders, according to Kathleen Merikangas, PhD, of the National Institute of Mental Health in Bethesda, Md., and colleagues.

Having both prolonged fatigue and a mood or anxiety disorder was associated with poorer physical and mental health and greater use of healthcare services compared with having only one of the disorders, the researchers reported online in the American Journal of Psychiatry.

"This suggests that the presence of fatigue may be used in clinical practice as an indicator of a more severe depressive or anxiety disorder," Merikangas and colleagues wrote.

Prolonged fatigue has been shown to be associated with social functioning and school attendance in adolescents and to overlap in many cases with mood and anxiety disorders in adults.

To explore the latter issue in youths, the researchers examined data from 10,123 teens who participated in the National Comorbidity Survey Adolescent Supplement, in which individuals were interviewed with a modified version of the World Health Organization's Composite International Diagnostic Interview.

The definition of prolonged fatigue was largely consistent with the ICD-10 definition for neurasthenia: extreme fatigue that lasts at least 3 months, does not respond to resting or relaxing, and is associated with at least one of several symptoms, including muscular aches and pains, dizziness, tension headache, sleep disturbance, inability to relax, or irritability.

Individuals with co-occurring mood disorders, generalized anxiety disorder, or panic disorder -- who are excluded from the ICD-10 definition -- were included in the current study.

Overall, 1.4% of the teens reported prolonged fatigue alone and 1.6% reported prolonged fatigue plus a depressive or anxiety disorder. Another 14.9% had a depressive or anxiety disorder alone.

The group with prolonged fatigue alone was generally similar to those with a depressive or anxiety disorder alone in terms of physical and mental health, and both groups were worse than the teens with neither disorder, "suggesting that fatigue states are themselves an important clinical entity," according to the researchers.

But in general, those with both prolonged fatigue and a depressive or anxiety disorder had the worst health status of any group.

The rate of severe or very severe disability, for example, was 80.9% among teens with both disorders compared with 59.2% in those with fatigue alone and 58.9% in those with a depressive or anxiety disorder alone.

Those with both disorders were also more likely to report the following:

Fair or poor mental health: 27.1% versus 18% for fatigue alone and 17.5% for depressive or anxiety disorder only

Fair or poor physical health: 32.1% versus 16% and 20.5%

Social phobia: 33.5% versus 11.5% and 14.4%

Substance use disorder: 36.4% versus 16.2% and 25.6%

In addition, the presence of both fatigue and a depressive or anxiety disorder was associated with greater use of health services in the prior year. For any mental health service, for example, the rate of use was 31.8% for teens with both disorders, 7.7% for those with fatigue alone, and 16.5% for those with a depressive or anxiety disorder.

"While from the perspective of illness severity these differences may appear appropriate, they also highlight the extent to which young persons with disabling fatigue only or anxiety/depressive syndromes only do not receive care," Merikangas and colleagues wrote.

"If less severe forms are risk states for the onset of the more severe comorbid form, as would be predicted by other adolescent and adult studies of these overlapping phenotypes, then the opportunity for secondary prevention of that later morbidity is not being addressed," they wrote.

They acknowledged that the study was limited by the possibility of recall bias in the assessment of lifetime disorders and by the cross-sectional design, which precluded the evaluation of temporal or longitudinal associations. Other limitations were the assessment of health service use based on parental reports for only a subset of the participants, and by differences between the definition of prolonged fatigue used and the definition of chronic fatigue syndrome.

The study was supported by NIMH Intramural Research Program grant Z01 MH- 002808-08 and, through the National Comorbidity Survey Adolescent Supplement (NCS-A) and the larger program of related NCS surveys, NIMH grant U01 MH-60220.

Co-author Femke Lamers, PhD, is supported by a Rubicon Fellowship from the Netherlands Organisation for Scientific Research (NWO) and by a Supplemental Intramural Research Training Award from the NIMH Genetic Epidemiology Research Branch.

Co-author Ian Hickie, MD, reported that 1) he currently serves on the board of the Psychosis Australia Trust (unpaid position) and on the Defence Mental Health Advisory Group (government committee); 2) he currently receives fees for consulting or reports from Bupa Australia (private health insurance) as a member of the Medical Advisory Panel; 3) he has received travel support in the last 5 years from Servier, AstraZeneca, PricewaterhouseCoopers, the American Psychiatric Association, Returned and Services League (RSL) National Congress, the Chinese Society of Psychiatry and Neurology, Australian General Practice Network, and Focus -- Sunshine Coast; 4) he has received research support in the last 5 years from Servier and Pfizer; 5) he has received payments for educational seminars or resources in the last 5 years from Servier, AstraZeneca, Pfizer (Wyeth), Eli Lilly, Broadcast Psychiatry, Janssen Cilag, Merck Sharp and Dohme, Elixir Healthcare Education, the Australian Mental Health Leadership Program, Australian Independent Schools of New South Wales, Australian Doctor Education, and Intelligence Squared Australia; 6) he previously had a business interest in St. George Neuropsychiatry Pty. (director); 7) he previously held positions at the Australian Department of Health and Ageing (sitting fee for the National Advisory Council on Mental Health), the Australian National Council on Drugs, and Headspace: the National Youth Mental Health Foundation (director on behalf of the University of Sydney, a member of the company); 8) he previously served on the following government advisory committees: Mental Health Expert Working Group (member), Access to Allied Psychological Services (member of expert advisory committee), National Advisory Council for Mental Health (member), and Common Approach to Assessment Referral and System Task Force co-convened by the Minister for Families, Housing, and Community Services (member); 9) he previously received payments for consulting, reports, or advisory work from Drinkwise Australia, Western Australia (Labor) Government, the Australian Department of Health and Ageing, Sydney Magazine, Sydney City Council, the Royal Australian and New Zealand College of Psychiatry, Wyeth, and Eli Lilly; 10) his partner Dr. Elizabeth Scott is Clinical Director of Headspace Camperdown and Campbelltown and previously had a business interest in Pearl 100, a partnership (ABN 55 251 484 962) trading as The Clinical Centre and registered to S. Duncan and St. George Neuropsychiatry Pty.; 11) mental health research conducted at the Brain & Mind Research Institute has been supported by Servier, Pfizer, the Heart Foundation, Beyond Blue, and the Bupa Foundation.

The other study authors report no financial relationships with commercial interests.

Reviewed by F. Perry Wilson, MD, MSCE Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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